It has become increasingly necessary to undertake pilot as well as more complete animal studies to support ongoing research of National Institute of Environmental Health Sciences (NIEHS) intramural investigators and in support of the testing efforts of the National Toxicology Program (NTP). In addition, the emergence and development of transgenic mice has offered alternatives to conventional animal models and a state-of-the-science approach to understanding the mechanisms of how environmental agents produce toxicity, including cancer. As new methodologies and techniques, such as means for quantitating cell proliferation and apoptosis or for measuring expression of growth factors, have become available, there has been an increasing demand for use of these methods. Therefore, the major objective of this contract is to examine animal model systems used in NTP bioassay studies and in in-house studies and to extend previous studies for additional information. The basic requirements of this contract are to generate tissue samples as a result of treating animals under defined protocols for analysis, to generate data on these samples, and to develop and characterize newer and better animal models that will be useful for study of environmental health risks.